Synergistically activating nucleophile strategy enabled organocatalytic asymmetric P-addition of cyclic imines.

Herein, we present an attractive organocatalytic asymmetric addition of P-nucleophiles to five-membered cyclic -sulfonyl imines facilitated by phosphonium salt catalysis, enabling the highly enantioselective synthesis of tri- and tetra-substituted cyclic phosphorus-containing benzosultams. With this protocol, various cyclic α-aminophosphonates were efficiently synthesized with high yields and exceptional enantioselectivities (up to >99% ee) under mild reaction conditions. The utility and practicality of this method were demonstrated through gram-scale reactions and straightforward elaborations.

Design and Analysis of 5-DOF Compact Electromagnetic Levitation Actuator for Lens Control of Laser Cutting Machine.

In laser beam processing, the angle or offset between the auxiliary gas and the laser beam axis have been proved to be two new process optimization parameters for improving cutting speed and quality. However, a traditional electromechanical actuator cannot achieve high-speed and high-precision motion control with a compact structure. This paper proposes a magnetic levitation actuator which could realize the 5-DOF motion control of a lens using six groups of differential electromagnets.

Phase separation of S-RNase promotes self-incompatibility in Petunia hybrida.

Self-incompatibility (SI) is an intraspecific reproductive barrier widely present in angiosperms. The SI system with the broadest occurrence in angiosperms is based on an S-RNase linked to a cluster of multiple S-locus F-box (SLF) genes found in the Solanaceae, Plantaginaceae, Rosaceae, and Rutaceae. Recent studies reveal that non-self S-RNase is degraded by the Skip Cullin F-box (SCF)-mediated ubiquitin-proteasome system in a collaborative manner in Petunia, but how self-RNase functions largely remains mysterious.

Calcium dobesilate-induced hyperpyrexia: A case report.

Rationale: Calcium dobesilate, a vasoprotective and antioxidant agent, is gradually being used for the treatment of chronic kidney disease. Calcium dobesilate-induced hyperpyrexia is a rare clinical event, and few studies have reported it.

Patient Concerns: The patient took calcium dobesilate, which caused high fever.

Performance and mechanism of sycamore flock based biochar in removing oxytetracycline hydrochloride.

In this study, sycamore flocs (SF), which caused environmental and health problems, were utilized to prepare biochar. SFB obtained under the conditions of activation agent KCO, pyrolysis temperature 900℃ and m(KCO):m(BC) 2 had the strongest adsorption capacity (730 mg/g) for oxytetracycline hydrochloride (OTC-HCl). The pseudo-second-order kinetic model and Langmuir model described the adsorption kinetics and isotherms best.

Enantioselective γ-Addition-Driven Cascade of β,γ-Unsaturated Ketones by Ion-Pair Catalysis: Access to Chiral 1,3-Dioxolochroman Scaffolds.

A highly enantioselective γ-addition-driven cascade of β,γ-unsaturated carbonyl compounds by bifunctional ion-pair catalysis has been developed. With this protocol, a range of functionalized chiral 1,3-dioxolochroman derivatives were prepared in high yields with superior stereoselectivities (>99% and >20:1 ). The utility of this method was demonstrated by one-pot synthesis, scaled-up preparation, and facile transformation.

Origin, loss, and regain of self-incompatibility in angiosperms.

The self-incompatibility (SI) system with the broadest taxonomic distribution in angiosperms is based on multiple S-locus F-box genes (SLFs) tightly linked to an S-RNase termed type-1. Multiple SLFs collaborate to detoxify nonself S-RNases while being unable to detoxify self S-RNases. However, it is unclear how such a system evolved, because in an ancestral system with a single SLF, many nonself S-RNases would not be detoxified, giving low cross-fertilization rates.

Regio- and Stereoselective Cascade of β,γ-Unsaturated Ketones by Dipeptided Phosphonium Salt Catalysis: Stereospecific Construction of Dihydrofuro-Fused [2,3-b] Skeletons.

Chiral (dihydro)furo-fused heterocycles are significant structural motifs in numerous natural products, functional materials and pharmaceuticals. Therefore, developing efficient methods for preparing compounds with these privileged scaffolds is an important endeavor in synthetic chemistry. Herein, we develop an effective, modular method by a dipeptide-phosphonium salt-catalyzed regio- and stereoselective cascade reaction of readily available linear β,γ-unsaturated ketones with aromatic alkenes, affording a wide variety of structurally fused heterocyclic molecules in high yields with excellent stereoselectivities.

Enantiodivergent Kinetic Resolution of 1,1'-Biaryl-2,2'-Diols and Amino Alcohols by Dipeptide-Phosphonium Salt Catalysis Inspired by the Atherton-Todd Reaction.

A highly enantiodivergent organocatalytic method is disclosed for the synthesis of atropisomeric biaryls via kinetic resolution inspired by a dipeptide-phosphonium salt-catalyzed Atherton-Todd (A-T) reaction. This flexible approach led to both R- and S-enantiomers by fine-tuning of bifunctional phosphonium with excellent selectivity factors (s) of up to 1057 and 525, respectively. The potential of newly synthesized O-phosphorylated biaryl diols was illustrated by the synthesis of axially chiral organophosphorus compounds.

Catalyst-Free Synthesis of α-Functionalized 2H-Chromenes in Water: A Tandem Self-Promoted pseudo-Substitution and Decarboxylation Process.

A catalyst-free decarboxylative reaction between β-keto acids and 2H-chromene acetals in water was developed. This reaction featured a broad substrate scope and easily obtainable starting materials to afford α-functionalized 2H-chromenes in high yields. The synthetic value of this protocol was also demonstrated by the scale-up synthesis and versatile conversions of the title product into other useful compounds.

Methylene Blue Attenuates Diabetic Retinopathy by Inhibiting NLRP3 Inflammasome Activation in STZ-Induced Diabetic Rats.

: This study aimed to investigate the regulatory effects of methylene blue (MB) on diabetic retinopathy (DR) and explored the molecular mechanisms of MB as a retina protection agent. : The thicknesses of retinal layers and permeability of the blood-retinal barrier (BRB) were measured by histology analysis, and the expression levels of NLRP3, ASC, procaspase-1, caspase-1, IL-1β, and IL-18 were measured by western blotting. Lentivirus-based knockdown of gene was used to confirm the role of NLRP3 inflammasome.

d-Glucosamine production from chitosan hydrolyzation over a glucose-derived solid acid catalyst.

A glucose-based solid acid catalyst (GSA) was synthesized by hydrothermal carbonization and its physicochemical properties were explored by various characterization techniques including IR, TG and SEM. In addition, its catalytic performance towards d-glucosamine formation from the hydrolysis of chitosan was extensively investigated to determine the effects of reaction parameters, such as reaction temperature, time and mass ratio of catalyst and reactants. The experimental results revealed that the yield of targeted product d-glucosamine could reach as high as 98.

Induction of Autophagic Death in Cancer Cells by Agonizing TR3 and Attenuating Akt2 Activity.

Apoptotic resistance is becoming a significant obstacle for cancer therapy as the majority of treatment takes the route of apoptotic induction. It is of great importance to develop an alternative strategy to induce cancer cell death. We previously reported that autophagic cell death mediated by nuclear receptor TR3 and driven by a chemical agonist, 1-(3,4,5-trihydroxyphenyl)nonan-1-one (THPN), is highly effective in the therapy of melanoma but not any other cancer types.

Cyclosporine nanomicelle eye drop: a novel medication for corneal graft transplantation treatment.

Corneal transplantation has been used to treat severe eye disease for decades, but the therapeutic effect of the operation is highly compromised by immunological allograft rejection. To improve the success rate of corneal transplantation, we studied the protective effects of cyclosporine nanomicelle eye drops (CNED) on immune rejection after high-risk corneal transplantation and its underlying mechanisms. The therapeutic effects against immune rejection of both conventional cyclosporine eye drop (CCED) and CNED in different concentrations were assessed and compared using animal models of corneal transplantation.

Impeding the interaction between Nur77 and p38 reduces LPS-induced inflammation.

Sepsis, a hyperinflammatory response that can result in multiple organ dysfunctions, is a leading cause of mortality from infection. Here, we show that orphan nuclear receptor Nur77 (also known as TR3) can enhance resistance to lipopolysaccharide (LPS)-induced sepsis in mice by inhibiting NF-κB activity and suppressing aberrant cytokine production. Nur77 directly associates with p65 to block its binding to the κB element.

Towards stereochemical control: A short formal enantioselective total synthesis of pumiliotoxins 251D and 237A.

A concise enantioselective synthesis of the advanced intermediate 5 for the synthesis of pumiliotoxins (Gallagher's intermediate) is described. The synthesis started from the regio- and trans-diastereoselective (dr = 98:2) reductive 3-butenylation of (R)-3-(tert-butyldimethylsilyloxy)glutarimide 14. After O-desilylation and Dess-Martin oxidation, the resulting keto-lactam 10 was subjected to a highly trans-stereoselective addition of the methylmagnesium iodide to give carbinol 11 as sole diastereomer.

Orphan nuclear receptor TR3 acts in autophagic cell death via mitochondrial signaling pathway.

Autophagy is linked to cell death, yet the associated mechanisms are largely undercharacterized. We discovered that melanoma, which is generally resistant to drug-induced apoptosis, can undergo autophagic cell death with the participation of orphan nuclear receptor TR3. A sequence of molecular events leading to cellular demise is launched by a specific chemical compound, 1-(3,4,5-trihydroxyphenyl)nonan-1-one, newly acquired from screening a library of TR3-targeting compounds.

Enantioselective total syntheses of (-)-FR901483 and (+)-8-epi-FR901483.

The enantioselective total syntheses of the potent immunosuppressant FR901483 (1) and its 8-epimer (47) have been accomplished. Our approach features the use of building block 6 as the chiron, the application of the one-pot amide reductive bis-alkylation method to construct the chiral aza-quaternary center (dr = 9:1), regio- and diastereoselective intramolecular aldol reaction to build the bridged ring, and RCM to form the 3-pyrrolin-2-one ring.

The orphan nuclear receptor Nur77 regulates LKB1 localization and activates AMPK.

Liver kinase B1 (LKB1) has important roles in governing energy homeostasis by regulating the activity of the energy sensor kinase AMP-activated protein kinase (AMPK). The regulation of LKB1 function, however, is still poorly understood. Here we demonstrate that the orphan nuclear receptor Nur77 binds and sequesters LKB1 in the nucleus, thereby attenuating AMPK activation.

Enantioselective syntheses of rigidiusculamides A and B: revision of the relative stereochemistry of rigidiusculamide A.

The first enantioselective synthesis of cytotoxic natural products rigidiusculamides A (ent-21) and B (8) has been achieved by two synthetic routes. The first one is convergent based on the common intermediate 11, obtained through a high yielding SmI(2) -mediated Reformatsky-type reaction. A highly diastereoselective one-pot Dess-Martin periodinane-mediated bis-oxidation allowed the direct conversion of the diastereomeric mixture of 11 into rigidiusculamide B (8).

A unique pharmacophore for activation of the nuclear orphan receptor Nur77 in vivo and in vitro.

Nur77 is a steroid orphan receptor that plays a critical role in regulating proliferation, differentiation, and apoptosis, including acting as a switch for Bcl-2 function. We previously reported that the octaketide cytosporone B (Csn-B) is a natural agonist for Nur77. In this study, we synthesized a series of Csn-B analogues and performed a structure-activity analysis that suggested criteria for the development of a unique pharmacophore to activate Nur77.

4-Bromo-2-chloro-aniline.

The title compound, C(6)H(5)BrClN, is almost planar (r.m.s.